AIMS/HYPOTHESIS: Non-invasive imaging of the pancreatic beta cell mass (BCM) requires the identification of novel and specific beta cell biomarkers. We have developed a systems biology approach to the identification of promising beta cell markers. METHODS: We followed a functional genomics strategy based on massive parallel signal sequencing (MPSS) and microarray data obtained in human islets, purified primary rat beta cells, non-beta cells and INS-1E cells to identify promising beta cell markers. Candidate biomarkers were validated and screened using established human and macaque (Macacus cynomolgus) tissue microarrays. RESULTS: After a series of filtering steps, 12 beta cell-specific membrane proteins were identified. For four of the proteins we selected or produced antibodies targeting specifically the human proteins and their splice variants; all four candidates were confirmed as islet-specific in human pancreas. Two splice variants of FXYD domain containing ion transport regulator 2 (FXYD2), a regulating subunit of the Na(+)-K(+)-ATPase, were identified as preferentially present in human pancreatic islets. The presence of FXYD2gammaa was restricted to pancreatic islets and selectively detected in pancreatic beta cells. Analysis of human fetal pancreas samples showed the presence of FXYD2gammaa at an early stage (15 weeks). Histological examination of pancreatic sections from individuals with type 1 diabetes or sections from pancreases of streptozotocin-treated Macacus cynomolgus monkeys indicated a close correlation between loss of FXYD2gammaa and loss of insulin-positive cells. CONCLUSIONS/ INTERPRETATION: We propose human FXYD2gammaa as a novel beta cell-specific biomarker.
AIMS/HYPOTHESIS: Non-invasive imaging of the pancreatic beta cell mass (BCM) requires the identification of novel and specific beta cell biomarkers. We have developed a systems biology approach to the identification of promising beta cell markers. METHODS: We followed a functional genomics strategy based on massive parallel signal sequencing (MPSS) and microarray data obtained in human islets, purified primary rat beta cells, non-beta cells and INS-1E cells to identify promising beta cell markers. Candidate biomarkers were validated and screened using established human and macaque (Macacus cynomolgus) tissue microarrays. RESULTS: After a series of filtering steps, 12 beta cell-specific membrane proteins were identified. For four of the proteins we selected or produced antibodies targeting specifically the human proteins and their splice variants; all four candidates were confirmed as islet-specific in human pancreas. Two splice variants of FXYD domain containing ion transport regulator 2 (FXYD2), a regulating subunit of the Na(+)-K(+)-ATPase, were identified as preferentially present in humanpancreatic islets. The presence of FXYD2gammaa was restricted to pancreatic islets and selectively detected in pancreatic beta cells. Analysis of human fetal pancreas samples showed the presence of FXYD2gammaa at an early stage (15 weeks). Histological examination of pancreatic sections from individuals with type 1 diabetes or sections from pancreases of streptozotocin-treated Macacus cynomolgus monkeys indicated a close correlation between loss of FXYD2gammaa and loss of insulin-positive cells. CONCLUSIONS/ INTERPRETATION: We propose human FXYD2gammaa as a novel beta cell-specific biomarker.
Authors: P Ylipaasto; B Kutlu; S Rasilainen; J Rasschaert; K Salmela; H Teerijoki; O Korsgren; R Lahesmaa; T Hovi; D L Eizirik; T Otonkoski; M Roivainen Journal: Diabetologia Date: 2005-07-01 Impact factor: 10.122
Authors: Martin Gotthardt; Georg Lalyko; Julliëtte van Eerd-Vismale; Boris Keil; Tino Schurrat; Michael Hower; Peter Laverman; Thomas M Behr; Otto C Boerman; Burkhard Göke; Martin Béhé Journal: Regul Pept Date: 2006-08-22
Authors: Shazia Adalat; Adrian S Woolf; Karen A Johnstone; Andrea Wirsing; Lorna W Harries; David A Long; Raoul C Hennekam; Sarah E Ledermann; Lesley Rees; William van't Hoff; Stephen D Marks; Richard S Trompeter; Kjell Tullus; Paul J Winyard; Janette Cansick; Imran Mushtaq; Harjeeta K Dhillon; Coralie Bingham; Emma L Edghill; Rukshana Shroff; Horia Stanescu; Gerhart U Ryffel; Sian Ellard; Detlef Bockenhauer Journal: J Am Soc Nephrol Date: 2009-04-23 Impact factor: 10.121
Authors: Yoshifumi Saisho; Paul E Harris; Alexandra E Butler; Ryan Galasso; Tatyana Gurlo; Robert A Rizza; Peter C Butler Journal: J Mol Histol Date: 2008-09-13 Impact factor: 2.611
Authors: J Hald; T Galbo; C Rescan; L Radzikowski; A E Sprinkel; H Heimberg; J Ahnfelt-Rønne; J Jensen; R Scharfmann; G Gradwohl; K H Kaestner; C Stoeckert; J N Jensen; O D Madsen Journal: Diabetologia Date: 2011-09-23 Impact factor: 10.122